Isopropyl carbamates derived from benzylamines provide isoindolinones by treatment with phosphorus pentoxide at room temperature. Utility of this Bischler-Napieralski-type cyclization and a new mechanism involving a carbamoyl cation for rationalization of this smooth conversion are discussed.

The lactonamycin model aglycon 4 was synthesized from the trihalogenated benzene derivative 10. Ethynyltetraol 6 was prepared from 10 via carbon elongations, oxidative demethylation, a cycloaddition reaction with the diene derived from homophthalic anhydride, and dihydroxylation. Final E- and F-ring constructions from 6 were realized via a palladium-catalyzed cyclization-methoxycarbonylation, a stereoselective methanol addition, and lactonization, leading to the production of 4.

2-Substituted 1,3-dithiane derivatives, (S)-1-(t-butyldiphenylsiloxy)-2-(1,3-dithian-2-yl)propane (9), (S)-1-(t-butyldimethylsiloxy)-2-(1,3-dithian-2-yl)propane, 1-(t-butyldiphenylsiloxy)-2-(1,3-dithian-2-yl)-2-methylpropane, and 1,2-bis(t-butyldiphenylsiloxy)-3-(1,3-dithian-2-yl)propane, were subjected to lithiation in THF with n-BuLi at room temperature (r.t.); the resulting anions reacted with 2,3-disubstituted oxirane, trans-2-methyl-3-(triphenylmethoxymethyl)oxirane (22), at r.t., giving the coupling products in satisfactory yield. On the other hand, the lithium salt formed in ether from (S)-2-(1,3-dithian-2-yl)-1-(4-methoxybenzyloxy)propane with n-BuLi at r.t. reacted with 22 at r.t. in the presence of hexamethylphosphoric triamide to afford the coupling product in moderate yield. In addition, a mixed organometallic reagent, n-BuLi / Bu2Mg, was found to be an effective metallation reagent for 9 and the resulting anion reacted with 22 to afford the coupling product in good yield.

2-Substituted-1,3-dithianes were subjected to lithiation by nBuLi at room temperature and the resulting anions reacted with 1,2-disubstituted epoxides at room temperature, giving the coupling products in satisfactory yield. In addition, a mixed organometallic reagent, n-BuLi/Bu 2 Mg, was found to be an effective metallation reagent for 2-substituted-1,3-dithianes.Since the introduction of 2-lithio-1,3-dithiane derivatives by Corey and Seebach in 1965, 1 synthetic organic chemists have been using them as the excellent acyl anion equivalents for carbon-carbon bond formation. 2 Representative examples are the coupling of 2-lithio-1,3-dithiane derivatives with epoxides. In general, 2-lithio-1,3-dithiane itself and 2-substituted-2-lithio-1,3-dithianes 1 (M = Li) react with monosubstituted epoxides 2 to afford the coupling products 3 in satisfactory yield (eq 1). Even in such a case, however, problems still remain; when anions are short-lived and/or epoxides are relatively poor electrophiles, the coupling reaction is capricious. 3 Moreover, it has been considered that 1,2-disubstituted epoxides 4 can not react efficiently with 2-substituted-2-lithio-1,3-dithianes 1 (M = Li, eq 2). Therefore, such coupling reactions have scarcely been attracted attention 4 and, to the best of our knowledge, have not been used in natural product syntheses. We now report in this letter the effective coupling reactions of 2-substituted-2-metallo-1,3-dithianes 1 with 1,2-disubstituted epoxides 4 at room temperature to afford the coupling products 5 in satisfactory yield. Compared with 3, the compound 5 includes the additional substituent R 3 in its structure. Therefore, in the case of 5 having the partial structure (R 1 = Me-branched unit, R 3 = Me: eq 2) such as A (eq 3), it would be possible to obtain a sequential array of alternate Me and OH groups, such as C, via de-dithioacetalization (A to B) and reduction (B to C). Equation 1, 2, 3We first selected 6 5,6 and 7 6,7 as a dithiane and a 1,2-disubstituted epoxide component, respectively (eq 4). t-BuLi in pentane (1 equiv for 6) was added at -78 °C to a solution of 6 in 10% HMPA-THF (0.2 M for 6) 8 and to this was added 7 (1 equiv for 6) in THF; the mixture was stirred at -78 °C for 1 d. But only the starting materials were recovered. n-BuLi/t-BuONa complex, which was used for metallation of 2-substituted-1,3-dithianes by Lipshutz, 9 was of no effect on this coupling at -78 °C. It was decided to investigate the lithiation conditions (in THF) by D 2 O quenching. Representative data are shown in Table 1. HMPA was needed for the anion generation at -78 °C by using n-BuLi or t-BuLi as a base (entries 1, 2, 6, and 7). Metallation with t-BuLi/HMPA and nBuLi/t-BuONa effectively occurred at -78 °C (entries 1 and 5). These results suggested that the inertness of the reaction of eq 4 was due to the poor electrophilicity of 7. We considered that it was necessary to raise the reaction temperature to overcome this problem. The use of HMPA in metallation at room temperature (rt: 20 -25 °C) was less sat...

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